TY  - JOUR
A1  - Wei, Xiaoyan
A1  - Franke, Julia
A1  - Ost, Mario
A1  - Wardelmann, Kristina
A1  - Börno, Stefan
A1  - Timmermann, Bernd
A1  - Meierhofer, David
A1  - Kleinridders, Andre
A1  - Klaus, Susanne
A1  - Stricker, Sigmar
T1  - Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis
JF  - Journal of cachexia, sarcopenia and muscle
N2  - Background Neurofibromatosis type 1 (NF1) is a multi-organ disease caused by mutations in neurofibromin 1 (NF1). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1-associated myopathy are mostly unknown. Methods To dissect the function ofNf1in muscle, we created muscle-specific knockout mouse models for NF1, inactivatingNf1in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analysed during prenatal and postnatal myogenesis and muscle growth. Results Nf1(Lbx1)and Nf1(Myf5)animals showed only mild defects in prenatal myogenesis. Nf1(Lbx1)animals were perinatally lethal, while Nf1(Myf5)animals survived only up to approximately 25 weeks. A comprehensive phenotypic characterization of Nf1(Myf5)animals showed decreased postnatal growth, reduced muscle size, and fast fibre atrophy. Proteome and transcriptome analyses of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High-resolution respirometry confirmed enhanced oxidative metabolism in Nf1(Myf5)muscles, which was concomitant to a fibre type shift from type 2B to type 2A and type 1. Moreover, Nf1(Myf5)muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1(Myf5)animals, in line with a drastic reduction of white, but not brown adipose tissue. Conclusions Our results demonstrate a cell autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross-tissue communication and mobilization of lipid reserves.
KW  - neurofibromatosis
KW  - NF1
KW  - myopathy
KW  - muscle atrophy
KW  - muscle metabolism
KW  - muscle fibre type
KW  - AMPK
Y1  - 2020
U6  - https://doi.org/10.1002/jcsm.12632
SN  - 2190-5991
SN  - 2190-6009
VL  - 11
IS  - 6
SP  - 1758
EP  - 1778
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Jia, Weihan
A1  - Anslan, Sten
A1  - Chen, Fahu
A1  - Cao, Xianyong
A1  - Dong, Hailiang
A1  - Dulias, Katharina
A1  - Gu, Zhengquan
A1  - Heinecke, Liv
A1  - Jiang, Hongchen
A1  - Kruse, Stefan
A1  - Kang, Wengang
A1  - Li, Kai
A1  - Liu, Sisi
A1  - Liu, Xingqi
A1  - Liu, Ying
A1  - Ni, Jian
A1  - Schwalb, Antje
A1  - Stoof-Leichsenring, Kathleen R.
A1  - Shen, Wei
A1  - Tian, Fang
A1  - Wang, Jing
A1  - Wang, Yongbo
A1  - Wang, Yucheng
A1  - Xu, Hai
A1  - Yang, Xiaoyan
A1  - Zhang, Dongju
A1  - Herzschuh, Ulrike
T1  - Sedimentary ancient DNA reveals past ecosystem and biodiversity changes on the Tibetan Plateau: overview and prospects
JF  - Quaternary science reviews : the international multidisciplinary research and review journal
N2  - Alpine ecosystems on the Tibetan Plateau are being threatened by ongoing climate warming and intensified human activities. Ecological time-series obtained from sedimentary ancient DNA (sedaDNA) are essential for understanding past ecosystem and biodiversity dynamics on the Tibetan Plateau and their responses to climate change at a high taxonomic resolution. Hitherto only few but promising studies have been published on this topic. The potential and limitations of using sedaDNA on the Tibetan Plateau are not fully understood. Here, we (i) provide updated knowledge of and a brief introduction to the suitable archives, region-specific taphonomy, state-of-the-art methodologies, and research questions of sedaDNA on the Tibetan Plateau; (ii) review published and ongoing sedaDNA studies from the Tibetan Plateau; and (iii) give some recommendations for future sedaDNA study designs. Based on the current knowledge of taphonomy, we infer that deep glacial lakes with freshwater and high clay sediment input, such as those from the southern and southeastern Tibetan Plateau, may have a high potential for sedaDNA studies. Metabarcoding (for microorganisms and plants), metagenomics (for ecosystems), and hybridization capture (for prehistoric humans) are three primary sedaDNA approaches which have been successfully applied on the Tibetan Plateau, but their power is still limited by several technical issues, such as PCR bias and incompleteness of taxonomic reference databases. Setting up high-quality and open-access regional taxonomic reference databases for the Tibetan Plateau should be given priority in the future. To conclude, the archival, taphonomic, and methodological conditions of the Tibetan Plateau are favorable for performing sedaDNA studies. More research should be encouraged to address questions about long-term ecological dynamics at ecosystem scale and to bring the paleoecology of the Tibetan Plateau into a new era.
KW  - Sedimentary ancient DNA (sedaDNA)
KW  - Tibetan Plateau
KW  - Environmental DNA
KW  - Taphonomy
KW  - Ecosystem
KW  - Biodiversity
KW  - Paleoecology
KW  - Paleogeography
Y1  - 2022
U6  - https://doi.org/10.1016/j.quascirev.2022.107703
SN  - 0277-3791
SN  - 1873-457X
VL  - 293
PB  - Elsevier
CY  - Oxford
ER  -